Our principal interest is in calcium metabolism of the myocardial cell in general and, in particular, the calcium metabolism of the cardiac sarcoplasmic reticulum. We have found that the calcium accumulation of the sarcoplasmic reticulum in cardiac muscle represents a complex binding release cycle with multiple independent sites undergoing a series of energy dependent transformations. Kinetic analysis has suggested a two component model for this calcium accumulation with one component linked to ATP-dependent calcium transport across the membrane. Because of the equilibrium between transported and superficially bound calcium modulation of cardiac contractility by factors which control calcium transport is considered highly likely. The mechanism by which this modulation occurs is a major source of our current investigation. We are currently concentrating on the examination of the role of phosphorylating mechanisms and cyclic AMP-dependent events. In addition, we have examined the relationship of other cytoplasmic structures which relate both geographically and biochemically to the sarcoplasmic reticulum. Our current investigation involves the characterization of a sarcoplasmic reticulum-glycogen complex with highly specific properties and the possible role of glycogenolysis in regulating calcium transport. In addition, we have recently described large quantities of microtubules found co-sedimenting with sarcoplasmic reticulum and also observed in intact cells to be in close proximity to sarcoplasmic reticulum. Cardiac tubulin is being characterized and its relationship to sarcoplasmic reticiulum evaluated. BIBLIOGRAPHIC REFERENCES: Schwartz, A., Entman, M.L., Kaniike, K., Lane, L.K., Van Winkle, W.B., and Bornet, E.: A spectrophotometric analysis of calcium uptake into sarcoplasmic reticulum of cardiac muscle and skeletal muscle (slow, fast and mixed) stimulated by cyclic AMP-dependent protein kinase and by phosphorylase b kinase: Relationship to phosphorylation. Biochimica et Biophysica Acta, 426:57-72, 1976. Entman, M.L., Kaniike, K., Goldstein, M.A., Nelson, T.E., Futch, T., and Schwartz, A.: Association of glycogenolysis with cardiac sarcoplasmic reticulum: A possible link between contractility and metabolic control. Journal of Biological Chemistry, 251:3140-3146, 1976.